This is a competitive renewal proposal describing a continuation of our program directed towards the total synthesis of brevetoxin B and hemibrevetoxin B. Both compounds are potent neurotoxins isolated from marine sources, and their synthesis is expected to be accompanied by discoveries in the area of new synthetic technologies and strategies and may have implications in biosynthesis, neurobiology, the environment and medicine. The crucial steps in the proposed syntheses involve the development and application of novel methods for the construction of 6-, 7- and 8- membered ring ethers based on bridging of dithionolactones or dithionoesters and ring closures of hydroxyketones or hydroxydithioketals.